Understanding How TicVac-U Anti-Tick Vaccine Works
Anti-tick vaccines have been used in other countries for effective tick control for some time. From Latin American countries such as Cuba, Brazil, Argentina, and Colombia, all the way to Australia, tick vaccines have formed the backbone of integrated tick control programs aimed at combating tick infestations and reducing chemical acaricides. The use of acaricides has become problematic in Uganda where they have become the main tick control method. Their potential to contaminate cattle meat, milk as well as the environment, combined with the emergency of acaricide-resistant tick strains, has put pressure on the government of Uganda to find an immunological solution to ticks, that does not pose a risk to human and animal health. Now, researchers at Makerere University COVAB have developed a new anti-tick vaccine in Uganda that can induce an immune response in cattle against common tick infestations.
A tick challenge
Ticks remain a major challenge as key vectors for the transmission of deadly tick-borne diseases in tropical and subtropical regions of the world. Currently, anti-tick control methods in Uganda have relied on the use of chemical or synthetic acaricides. However, the uptick in resistance among tick populations to common acaricide drugs, as well as acaricide contamination of the environment and food products, has necessitated an alternative tick-control method, of which anti-tick vaccines offer the best solution. Tick vaccines in other countries so far have proven to be safer, sustainable, environmentally friendly and cost-effective.
However, a broadly effective anti-tick vaccine for common tick vectors has remained elusive. This is isn’t surprising since there are over 825 described tick species in the world.
What kind of ticks are in Uganda?
The most common tick species in Uganda are R. appendiculatus (Brown ear tick), R. decoloratus (blue tick) and A. variegatum (bont legged tick). These three are the most economically significant tick vectors in Uganda, responsible for a staggering 89% of the most prevalent and debilitating cattle tick infestations in Uganda, including East Coast Fever (theileriosis), Babesiosis (red urine), Anaplasmosis (gall sickness) and Heartwater (Cowdria).
These tick-borne diseases are responsible for staggering economic losses estimated at approximately US$ 1.1 billion every year, arising from the treatment of the parasitic disease burden, loss of investment opportunities in the cattle value chain and losses due to fatalities. The R. appendiculatus, the brown ear tick which transmits Theileria parva East Coast Fever, on its own contributes to almost 60% of losses in beef production and 48% of losses in milk production recorded in Uganda.
Is there a vaccine for tickborne East Coast Fever?
A tick vaccine against East Coast Fever and R. appendiculatus remains elusive. To date, the only practical preventative solution to East Coast Fever, akin to a vaccine, has been the unconventional Infection and Treatment method (ITM) developed in the 1970s. It’s not used in Uganda because it’s expensive for smallholder farmers and also it’s very difficult to produce, store or distribute, which has limited its viability for large-scale deployment.
The feasibility of using recombinant proteins against cattle ticks has already been demonstrated with commercially available anti-vaccines based on glycoproteins (Bm86 proteins) such as TickGARD® (Australia), Gavac® (Cuba) and Go-Tick® (Colombia), which have successfully been used to control R. microplus ticks.
However, these anti-tick vaccines have shown low efficacy in the control of R. appendiculatus and other local tick species. This is because they use recombinant proteins based on Bm86 which has shown little efficacy against local cattle ticks. These vaccines simply aren’t developed for ticks and tick-borne diseases in Uganda or Africa in mind.
This isn’t a new problem for Africa.
Let’s take the example of East Coast Fever. It kills over 1 million cattle annually in Africa. It is considered the most fatal, most diagnosed and economically important cattle disease in many African countries including Uganda. It kills infected cattle within a matter of weeks. It is especially deadly to untreated exotic cattle, where the mortality rate can be 100%. It is also the leading killer of local calves in Uganda.
Yet surprisingly, a disease that kills so much livestock has not received the attention it deserves from the global animal health industry. This is hardly surprising though as tropical diseases affecting people or animals in underdeveloped economies have historically received little attention.
But this narrative is changing. Since the COVID-19 pandemic, vaccine development and the pathogen economy have been prioritised by the government of Uganda.
Anti-tick vaccine breakthrough
Now, veterinary researchers from Makerere University College of Veterinary Medicine, Animal Resources and Bio-Security (CoVAB), led by Dr. Margaret Saimo-Kahwa have been working on a new anti-tick vaccine candidate – TicVac-U, that can induce an immune response in cattle via activation of antibodies. Once these antibodies are activated in immunized cattle, they incapacitate ticks' ability to feed, reproduce, and lay eggs, thus protecting cattle against common tick infestations like East Coast Fever, Babesiosis and Anaplasmosis.
The research team, which includes other renowned Makerere University scientists including Dr Kokas Ikwap, Dr William Olaho, Dr David A. Kalenzi, Dr Ann Nanteza, Dr Peregrine Sebulime, and many others, have been working on using recombinant tick gut proteins identified from various local ticks in Uganda and East Africa, as a way of creating a locally produced anti-tick vaccine capable of targeting multiple ectoparasites.
What the Principal Investigator says
“The protein (Ra86) identified from R. appendiculatus ticks found in Uganda and East Africa; this gene occurs in two variant forms, either Ra92A or Ra85A in individual ticks in the field” said Dr. Margaret Saimo-Kahwa, the Principal Investigator, Presidential Anti-Tick Vaccine Development Initiative.
“Our sequences of the tick gut protein variants (Ra92A and Ra85A) were synthesized and put into “Pichia pastoris” strain of yeast cells" Dr. Saimo-Kahwa further remarked.
“The Ra86 protein is localized in the tick gut and it is a concealed antigen, meaning it’s hidden from the host’s immune system during normal tick feeding. As ticks feed and become engorged with the blood meal from vaccinated cattle, host antibodies damage tick gut walls, resulting in death or diminished reproductive capacity” Dr. Saimo-Kahwa said.
In stall experiments on Ra86 vaccinated cattle, the impact on nymphs and adult R. appendiculatus ticks after feeding was examined. Results showed that molting of nymphal ticks to the adult stage was significantly reduced in ticks feeding on Ra86 vaccinated cattle in comparison to the control group. There was a reduction in the number of ticks on hosts by 69.7%, stopping attachment of ticks by 60%, and reduced egg-laying capacity of the ticks by 50%.
Dead nymphs (encircled) compared to the moulted young and unfed adult (with legs seen)
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Furthermore, vaccination with Ra86 lowered Theileria parva parasites in vaccinated cattle, a significant outcome since it is T. parva parasites that cause East Coast fever. Transmission of these parasites was diminished as a result of vaccination, lowering East Coast Fever clinical cases, while still advantageously enabling the establishment of immune protection in immunized cattle, underscoring the Ra86-based vaccine as a very promising vaccine for tick-borne East Coast Fever.
The team is currently embarking on the mass production of TicVac-U vaccine batches in yeast cells in-line at Alfasan Uganda, a vaccine production facility with cGMP compliance. Once the promising candidate vaccine has been mass-produced, it will undergo final clinical trials in live field conditions for assessment in cattle before commercial vaccine production begins.
“My team has so far built the technological capacity to produce these protein variants and formulate them into a candidate vaccine.” “Once we mass produce these batches from our specialized vaccine line, we aim to test them in field conditions from different geographical regions of Uganda to improve candidate vaccine efficacy such that it is highly efficacious and effective against all important tick species in the country” Dr. Saimo further commented.
Going forward, the TicVac-U team hopes that the Ra86-based anti-tick vaccine will become the backbone of integrated tick management and control strategies in Uganda and East Africa in a similar fashion Bm86 based commercial anti-vaccines such as TickGARD®, and Gavac® were successfully used in Latin America to control tick infestations and reduce chemical acaricide use.
